We have examined thymic influence on the MHC-specificity expressed by functionally and phenotypically distinct T cell subsets. These studies have indicated a hitherto unappreciated role of nominal self antigens in thymic selection of the developing T cell repertoire. Studies on thymocytes from genetically defective scid mice have suggested a relationship between TcR gene arrangement and expression of CD4/CD8 accessory molecules in thymocyte differ- entiation. Studies with thymic organ cultures have revealed that it is possible to generate functionally competent T cells from fetal liver stem cells in vitro.